Dual topology of functional Toll-like receptor 3 expression in human hepatocellular carcinoma: Differential signaling mechanisms of TLR3-induced NF-κB activation and apoptosis

  • Authors:
    • Kentaro Yoneda
    • Kazushi Sugimoto
    • Katsuya Shiraki
    • Junichiro Tanaka
    • Tetsuya Beppu
    • Hiroyuki Fuke
    • Norihiko Yamamoto
    • Masahiro Masuya
    • Ryo Horie
    • Kazuhiko Uchida
    • Yoshiyuki Takei
  • View Affiliations

  • Published online on: November 1, 2008     https://doi.org/10.3892/ijo_00000080
  • Pages: 929-936
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Toll-like receptor 3 (TLR3) is a pattern-recognizing receptor that is involved in immune signaling and plays a crucial role in survival by being able to recognize various viral components including double-stranded RNA (dsRNA). TLR3 expression and function in cancer cells are not well understood. We investigated the expression of TLR3 in hepatocellular carcinoma (HCC) cells and the function of TLR3 signaling by stimulation and transfection with polyinosinic-polycytidylic acid (Poly I:C), a synthetic form of dsRNA. TLR3 mRNA was expressed in HCC tissues as well as in non-tumor tissues. Positive immunohistochemical staining for TLR3 was observed in 52.7% of HCC tissues, and in HCC cells we found both membranous and cytoplasmic expression of TLR3. While cell surface stimulation of TLR3 with Poly I:C did not affect cell viability, it did activate NF-κB levels. In contrast, cytoplasmic stimulation with transfected Poly I:C significantly induced apoptosis accompanied by the down-regulation of anti-apoptotic protein. Transfected Poly I:C also synergistically augmented TRAIL-induced apoptosis, but only with low levels of transfected Poly I:C was IFN-β production not observed. In conclusion, our results indicate that TLR3 expression in HCC plays an important role with regard to cell survival and proapoptotic activity. Endogenously expressed TLR3 may provide new clinical prospects for TLR3 agonists as cytotoxic agents in HCC.

Related Articles

Journal Cover

November 2008
Volume 33 Issue 5

Print ISSN: 1019-6439
Online ISSN:1791-2423

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Yoneda K, Sugimoto K, Shiraki K, Tanaka J, Beppu T, Fuke H, Yamamoto N, Masuya M, Horie R, Uchida K, Uchida K, et al: Dual topology of functional Toll-like receptor 3 expression in human hepatocellular carcinoma: Differential signaling mechanisms of TLR3-induced NF-κB activation and apoptosis. Int J Oncol 33: 929-936, 2008.
APA
Yoneda, K., Sugimoto, K., Shiraki, K., Tanaka, J., Beppu, T., Fuke, H. ... Takei, Y. (2008). Dual topology of functional Toll-like receptor 3 expression in human hepatocellular carcinoma: Differential signaling mechanisms of TLR3-induced NF-κB activation and apoptosis. International Journal of Oncology, 33, 929-936. https://doi.org/10.3892/ijo_00000080
MLA
Yoneda, K., Sugimoto, K., Shiraki, K., Tanaka, J., Beppu, T., Fuke, H., Yamamoto, N., Masuya, M., Horie, R., Uchida, K., Takei, Y."Dual topology of functional Toll-like receptor 3 expression in human hepatocellular carcinoma: Differential signaling mechanisms of TLR3-induced NF-κB activation and apoptosis". International Journal of Oncology 33.5 (2008): 929-936.
Chicago
Yoneda, K., Sugimoto, K., Shiraki, K., Tanaka, J., Beppu, T., Fuke, H., Yamamoto, N., Masuya, M., Horie, R., Uchida, K., Takei, Y."Dual topology of functional Toll-like receptor 3 expression in human hepatocellular carcinoma: Differential signaling mechanisms of TLR3-induced NF-κB activation and apoptosis". International Journal of Oncology 33, no. 5 (2008): 929-936. https://doi.org/10.3892/ijo_00000080